METHOD OF USE OF ACTIVATED FUNCTIONAL PROTEINS TO IMPROVE ANIMAL HEALTH

Abstract

It was found that feeding a composition including activated growth factor(s) increases feed to gain ratio, increases overall weight gain, reduces necessary antibiotic or electrolyte therapy and reduces mortality in animals. The composition is derived by first separating growth factor(s) from a source such as whey or blood, then subjecting the factor to an activation process, and then providing the activated growth factor to the animal. A feed additive comprising activated growth factors in appropriate amounts, shows results that are an improvement over standard therapies of supplementation. Application of activated growth factors may be by topical, injection or oral application.

Claims

1. A method of using activated functional proteins to improve at least one animal health metric selected from a group consisting of weight gain, feed intake, teed efficiency, growth less medical and lower mortality said method comprising the step of administering an effective amount of at least one activated functional protein wherein the level of activation of said activated function protein is above the level found in a biological source of said at least one functional protein.

2. A method of using at least one activated functional protein to produce an improved animal supplement comprising mixing with a conventional supplement an effective amount of the at least one activated functional protein wherein the level of activation of said at least one activated functional protein is above the level found in a biological source of said at least one functional protein.

3. The method of claim 1 wherein the level of activation of said at least one functional protein is increased above the level of activation of said at least one functional protein found in said biological source by a method selected from a group consisting of pH adjustment, temperature adjustment, alcohol extraction, enzyme addition, ionic change, chemical addition, and pressure changes.

4. The method of claim 1 wherein the level of activation of the at least one functional protein is increased above the level of activation of said at least one functional protein found in said biological source by heat shock.

5. The method of claim 1 wherein said activated functional proteins are fed neonatal animals.

6. A method of producing an improved animal feed for supplementing the diet of an animal comprising the steps of mixing a conventional feed with a material containing at least one activated functional protein derived from a biological source wherein the level of activation of said at least one activated functional protein is higher than the level of activation of said functional protein in the biological source.

7. A composition for reducing the mortality rate of young animals comprising effective amounts of a material comprising a level of activation of at least one activated functional protein higher than a biological source of the at least one activated functional protein.

8. A method for improving the health of neonatal calves comprising providing an effective amount of at least one activated growth factor to a neonatal calf within six hours of birth.

9. A method for improving the health of young calves comprising providing an effective amount of at least one activated growth factor to a calf within three days of birth.

10. A method for improving growth of young pigs comprising improving feed to gain ratio by providing a composition comprising an effective amount of at least one activated growth factor.

11. A method for improving growth of young pigs comprising increasing average daily gain by providing a composition comprising an effective amount of at least one activated growth factor.

12. The method of claim 1 wherein the step of administering comprises using said effective amount of at least one activated functional protein as a feed supplement.

13. The method of claim 1 wherein the step of administering comprises dosing the effective amount of at least one activated functional protein as an oral medicinal application.

14. The method of claim I wherein the step of administering comprises applying the effective amount of at least one activated functional protein as a topical application.

15. The method claimed in claim 1 wherein the step of administering comprises applying the effective amount of at least one activated functional protein as an injected medicinal application.

16. The method claimed in claim 1 wherein said animal is selected from the group consisting of: bovine, porcine, equine, canine, feline, poultry, human, and aquacultured animals.

Description

BRIEF DESCRIPTION O THE DRAWINGS

[0026] FIG. 1 Swine trials Phase 1 diet:

[0027] FIG. 2 Swine trials Phase 2 diet

[0028] FIG. 3 Days 0-21 chart comparing daily gain, daily feed intake, feed to gain ratios

[0029] FIG. 4 Days 0-43 chart comparing daily gain, daily feed intake, feed to gain ratios

[0030] FIG. 5 Chart neonatal bovine trials

DETAILED DESCRIPTION OF THE INVENTION

[0031] Functional proteins including growth factors were present in plasma purchased commercially, and activated (for an example of an activation process, see Example 3 below), and thereafter dried. The activated growth factors were administered as described in several trials and results were collected. In the Examples below, the terms 1/x diet or 1/x functional proteins or growth factors diet refers to a diet wherein functional proteins and growth factors are fed at a rate that is 1/x that fed of plasma in the plasma diet. In other words, if the plasma diet includes X amount of plasma, then the 1/x diet includes an amount of functional proteins including growth factors that is 1/x the amount of plasma in the plasma diet. The difference in mass and protein was made up with nutirtional protein supplements, often soy derived.

Example 1Titration Trial

[0032] Titration trials were conducted. Referring now to FIGS. 1 and 2, a study of 192 pigs, with an average start weight o 10.8 lbs. was conducted. The study was set for 2 pigs/pen, 16 replicates per treatment. The activated functional proteins diets were fed for (4 days as was a control diet, and a plasma diet. Thereafter all pigs were fed the same diet (see FIGS. 1 and 2). The functional proteins diets were set to include activated functional proteins at specified weight ratios relative to plasma in the plasma diet. The functional proteins diets did not include plasma; however, the protein equivalent of the plasma was added in the form of soy protein isolate. The control diet did not include plasma or activated functional proteins. The results shown in FIG. 3 indicate that the average daily gain for days 0-7 was statistically higher (p<0.05) for the activated functional proteins diet at 1/5 the weight of plasma in the plasma diet. The average daily feed intake in the 1/5 and 1/15 functional proteins diets were statistically higher than for the control diet, but feed intake only for the 1/5 diet was statistically higher than the plasma diet. As a result of these differences, the feed to gain ratios for all of the functional proteins diets were lower than for either the control or the plasma diet for days 0-7, specifically the 1/5 diet. For days 8-21, average daily gain and average daily feed intake were only slightly higher for the activated functional proteins diets, with the 1/5 and 1/15 diets highest. Feed to gain ratios followed suit. Results, overall, for days 1-21 and, again, for days 1-43 are shown in FIG. 4. Average daily gain for the 1/5 and 1/15 functional proteins diet was statistically higher than the plasma diet for days 0-21; average daily gain for the 1/15 functional proteins diet was higher for days 0-43.

Example 2(5)Calves Mortality and Treatment

[0033] In this study, 150 calves between 0-3 days old were randomly allotted in a single blind study. There were three groups; negative control, competitor colostrum supplement, and the functional proteins blend. The study tracked weight gain, mortality and quantity of antibiotic/electrolyte treatments. The colostrum supplement and the functional proteins blend (2 grams blended with standard milk replacer to normal dose weight) replaced the first standard milk replacer bottle feeding for those respective experimental groups; thereafter, all calves were fed the same standard milk replacer. Weight gain for the activated functional proteins group was higher than the other groups while mortality was less than half that of the colostrum supplement or the negative control. The number of antibiotic and electrolyte treatments required for the activated functional proteins group was only 70% the number required for the colostrum group, and only 61% of the number required by the negative control. (see FIG. 5)

Example 3Method to Obtain Activated Growth Factors

[0034] Activated growth factors may be obtained as known in the prior art via pressure, pH activation, enzyme addition, ionic changes, other chemical treatment or heat shock following standard protocols. See Physicochemical Activation of Recombinant Latent Transforming Growth Factor-beta's 1,2, and 3, Brown, Peter D., Wakefield, Lalage M., Leninson, Arthur D., Sporn, Micheal B. (1990) Growth Factors, Vol. 3, pp. 35-43.

[0035] In the present invention, functional proteins were not separated from the biological starting material employing one of many methods known in the art but were, instead, purchased from a commercial supplier.

[0036] The growth factors were then activated by two of the aforementioned methods as described by Brown et al. In one application, pH was adjusted from the starting material's natural pH until measurements of activation of functional proteins showed an increase in activation above the activation at the natural pH. As known in the prior art, the pH adjustment used may he either basic or acidic with sharp transitions from latency between pH 4.1 and 3.1 and between pH 11.0 and 11,9 as reported by Brown et al. for both TGF-1 and 2. As is also well known, adjustments can be achieved via standard addition of NaOH, HCl or other bases and acids.

[0037] The second activation method used included heat shocking the commercially obained proteins to 75 degrees Celsius, holding for five (5) minutes or to 80 degrees Celsius for 1 minute, or until measurements of activation of functional proteins showed increase in activation above natural state. In this example, the time periods cited were sufficient, albeit longer time periods at 75 degrees showed no negative effects; up to an hour at 50-60 degrees celsius was also useful.

[0038] Activation of certain functional proteins by the aforementioned methods was confirmed by ELISA assay (R&D Systems, Minneapolis, Minn.). The level of activated IGF-1 was measured for the plasma source employed in the above-described pig trials and also measured in the preparation of activated functional proteins obtained as described above. In each situation, the activated IGF1 in the sample was first measured prior to subjecting the sample to the assay protocol (X) and then measured after being subjected to the assay protocol (Y). The measurements are expressed as X/Y. Specifically, when the plasma source was Innomax Plasma, from Land O'Lakes the results were as follows: [0039] Innomax IGF-1 measurements, three results were: [0040] 35/581, 25/686, 37/573 activated/total in ng/g. [0041] Measurements of prepared activated IGF-1 were: [0042] 150/695, 119/396, 244/364 activated/total in ng/g.

[0043] It is important to understand that the assay was used in a fairly unique manner. As noted above, the first measurement was made without subjecting the sample to a an activation process. The pH change required by the ELISA protocol is used to activate the functional proteins so, theoretically, if the pH treatment step required by the ELISA protocol is skipped, the resultant measurement should be indicative of the level of activation of the growth factors in the sample. The second measurement was made after the sample was subjected to the extreme pH which is part of the ELISA protocol. Theoretically, this extreme pH should result in activation of all of the growth factors.

[0044] Thus, the present invention has been described in an illustrative mariner. It is to be understood that the terminology that has been used is intended to be in the nature of words of description rather than of limitation.

[0045] Many modifications and variations of the present invention are possible in light of the above teachings. Therefore, within the scope of the appended claims, the present invention may be practiced otherwise than as specifically described.